INHALABLE RAPAMYCIN FORMULATION FOR TREATING AGE-RELATED CONDITIONS
The present invention relates to methods and compositions for anti-aging therapy and for the treatment and prophylaxis of age-related diseases and disorders in a human subject in need of such therapy or treatment, the methods comprising the pulmonary administration to the subject, preferably via inhalation, of composition comprising rapamycin, or a prodrug or derivative thereof.
1 . A pharmaceutical composition in the form of an inhalable dry powder comprising microparticles of a rapamycin derivative or analogue and particles of a carrier, wherein the rapamycin derivative or analogue is selected from the group consisting of everolimus, temsirolimus, ridaforolimus, umirolimus and zotarolimus.
2 . The pharmaceutical composition of claim 1 , wherein the amount of rapamycin derivative or analogue in the composition is from 0.1% to 20% (w/w) or from 0.25% to 2% (w/w), based upon the total weight of the composition.
3 . The pharmaceutical composition of claim 1 , wherein the microparticles of rapamycin derivative or analogue have an MMAD of from 2 to 3 microns.
4 . The pharmaceutical composition of claim 1 , wherein the carrier is selected from the group consisting of arabinose, glucose, fructose, ribose, mannose, sucrose, trehalose, lactose, maltose, starches, dextran, and mannitol.
5 . The pharmaceutical composition of claim 1 , wherein the particles of the carrier have diameters ranging from 1 to 200 microns, from 30 to 100 microns, or less than 10 microns.
6 . The pharmaceutical composition of claim 1 , wherein the carrier is a blend of two different carriers, a first carrier and a second carrier.
7 . The pharmaceutical composition of claim 6 , wherein the first carrier comprises of particles having diameters ranging from 30-100 microns and the second carrier comprises particles having diameters of less than 10 microns.
8 . The pharmaceutical composition of claim 6 , wherein the carrier comprises a blend of two different lactose carriers.
9 . The pharmaceutical composition of claim 1 , wherein the rapamycin derivative or analogue has an isomeric B:C ratio of greater than 30:1 or greater than 35:1.
10 . The pharmaceutical composition of claim 1 , comprising a surfactant additive selected from polyethylene glycol (PEG)-fatty acids and PEG-fatty acid mono and diesters, PEG glycerol esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar and its derivatives, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene (POE-POP) block copolymers, sorbitan fatty acid esters, ionic surfactants, fat-soluble vitamins and their salts, water-soluble vitamins and their amphiphilic derivatives, amino acids and their salts, and organic acids and their esters and anhydrides.
11 . A pharmaceutical composition in the form of an inhalable dry powder consisting essentially of microparticles of rapamycin derivative or analogue and particles of a carrier, wherein the microparticles of rapamycin derivative or analogue comprises particles having a Mass Median Aerodynamic Diameter (MMAD) of from 1 to 5 microns, and wherein the rapamycin derivative or analogue is selected from the group consisting of everolimus, temsirolimus, ridaforolimus, umirolimus and zotarolimus.
12 . The pharmaceutical composition of claim 11 , wherein the carrier is a lactose carrier or a blend of two different lactose carriers.
13 . The pharmaceutical composition of claim 12 , wherein the microparticles of rapamycin derivative or analogue have an MMAD of from 2 to 3 microns.
14 . The pharmaceutical composition of claim 13 , comprising a surfactant additive selected from polyethylene glycol (PEG)-fatty acids and PEG-fatty acid mono and diesters, PEG glycerol esters, alcohol-oil transesterification products, polyglyceryl fatty acids, propylene glycol fatty acid esters, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar and its derivatives, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene (POE-POP) block copolymers, sorbitan fatty acid esters, ionic surfactants, fat-soluble vitamins and their salts, water-soluble vitamins and their amphiphilic derivatives, amino acids and their salts, and organic acids and their esters and anhydrides.
15 . The pharmaceutical composition of claim 1 , wherein the composition does not contain a surfactant or other additives.
16 . The pharmaceutical composition of claim 11 , wherein the composition does not contain a surfactant or other additives.
17 . A method for treatment and prophylaxis of age-related diseases and disorders in a human subject in need of such treatment or prophylaxis, the method comprising administering to the subject via inhalation a composition of claim 1 .